This program project is designed to characterize gene products in the developing human fetus and to develop techniques for discovering and characterizing potential exogenous agents which might disturb the normal processes of differentiation. The technique of in vitro fertilization of mammalian ova and maintainence in vitro to the blastula stage provides a unique opportunity to study mutagenesis and development with precision, as well as to study genetic transformation through microinjections of nuclei, whole chromosomes and DNA into these mammalian embryos. Direct studies of fetal tissues and cultured fetal cells have been designed to characterize fetal enzymes, quantitatively and qualitatively, in order to increase the precision of prenatal detection and to shed light on the basic enzymatic defects in hereditary metabolic diseases, especially those associated with lysosomal hydrolase deficiencies and aberrations of porphyrin metabolism. Production of inter and intra species cultured hybrid cells have further characterized these enzymatic defects and provide data on complementation, linkage and enzyme induction. The effects on the fetus of maternally ingested drugs will be investigated in fetal cells and tissues and complementary cytogenetic monitoring may lead to more precise testing procedures for mutagenic effects. Studies of development of mechanisms for resistance to infections (immunoglobulin production, polymorphonuclear response) may lead to techniques of prenatal detection of deficiencies in these processes and to detection of fetuses infected by viruses in utero.